                1. All references cited herein are incorporated by reference in their entirety as though fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.        
Clinical problems in muscle occur at the extremes of contraction. Painful excessive or continuous contractions (spasms or cramps) are common as well as inadequate contraction of gastrointestinal sphincters leading to undesireable leakage. Drug treatment typically target specific receptors such as acetylcholine(cholinergic), but due to the widespread location of such receptors in the body, have diverse side effects. Adverse side effects have made drug therapy ineffective for many. What is taught here is a non-drug method based on portable externally applied magnetic, radiofrequency burst, and light stimulation targeting non-cholinergic receptors to modulate gastrointestinal smooth muscle and other muscle contraction. Portability and external application makes targeting of specific body problem areas possible non-invasively. In this way adverse reactions due to secondary effects can be minimized. Contraction or relaxation can be promoted by adjusting stimulation parameters. One embodiment of the proposed new device is treatment of the gastrointestinal system, but similar clinical problems are faced in the lungs and airway and can be treated in a similar way. The main differences for the airways are the specific smooth muscle fiber types and primary focus on relaxation responses. Smooth muscle is also located in every blood vessel of the body including the heart and lungs so similar cardiovascular problems may also be targeted. Pulmonary hypertension results when lung blood vessels are excessively constricted which can lead to pulmonary edema and gas exchange problems. Stimulation as described herein targeting lung vascular smooth muscle relaxation could be used as treatment to reduce pulmonary artery pressure. By limiting the treatment area of the applied stimulation to the lungs, a general systemic blood pressure effect can be avoided. The unique advantage of external magnetic, radiofrequecy burst, and light stimulation for treatment of the lungs is the simultaneous improvement of ventilation (bronchodilation) and perfusion (vasodilation) together. It is well known that the ratio of ventilation and perfusion in the lungs correlates with gas exchange. The more uniformly matched ventilation is to perfusion the better the gas exchange. The current inventive device then offers a means of improvement of gas exchange in a diseased lung where non-uniformity of ventilation perfusion ratio is a problem. Such non-uniformity is known to those skilled in the art to be a major clinical cause of low blood oxygenation. The non-cholinergic non-adrenergic receptors (NANC) targeted by the inventive device stimulation include the purinergic receptors which are linked to adenosine triphosphate(ATP) release as well as nitrergic receptors linked to nitric oxide . ATP applied externally is known to both enhance (diaphragm) and reduce (limb muscle) contraction force of skeletal muscle. Specific possible applications of the current inventive device are the relaxation of a cramped limb skeletal muscle and enhancing muscle contraction of the diaphragm of a patient suffering from respiratory insufficiency. ATP and purinergic receptors have also been found previously to have significant effects on diverse body functions such as cardiac function and mucus production. Intravenous ATP can depress cardiac muscle electrical conduction for suppression of arrhythmias. Mucus production in the eye and airways can be increased by ATP. Inadequate mucus liquid production occurs in cystic fibrosis where mucus is too thick for adequate clearance and during dry eye. Thus the potential clinical applications of the current inventive device go well beyond the specific application examples presented here for smooth and skeletal muscle problems. In different prior examples of negative responses connected with ATP administration it is important to note that as shown specifically for smooth muscle in the example described later, the specific pattern of administration and strength of stimulation could possibly reverse the negative to a positive effect. Nitric oxide is a well known smooth muscle relaxant, but has also been identified as being responsible for the “off” contraction following electrical stimulation of smooth muscle. Nitric oxide during electrical stimulation is known to cause a significant relaxation response especially in certain types of pre-contracted smooth muscle. Both purinergic and nitrergic receptors can be targeted by the current inventive device for specific applications.
The most common functional gastrointestinal problem is irritable bowel syndrome (IBS) which affects about 14% of the US population(Hungin 2005)). Abdominal pain and discomfort typically prompts consultation and drug therapy using antispasmotics or smooth muscle relaxants. Up to 68% of patients complained of side effects when given the high dose of antispasmotics required to improve pain (Lacy 2009). Thus, effectiveness of current therapy is limited. Antispasmotics affect cholinergic receptors which are present in all smooth muscle. Relaxing a contracted intestine can also relax sphincters and lead to undesirable leakage on either or both ends of the gastrointestinal tract.
Asthma affects about 8% of the US population and airway smooth muscle contraction leads to the need for treatment. Smooth muscle relaxants are used in treatment with a similar set of side effects as for gastrointestinal use. It should be emphasized that both constriction and dilation is possible by the inventive device stimulation and that only by careful adjustment of stimulation parameters can dilation be insured. Related to this is the known contraindication of administering intravenous ATP to asthmatics due to provoking possible bronchoconstriction. It is postulated that ATP can be involved in mediating bronchodilation as well, the pattern of stimulation leads to the difference in response.
Electrical stimulation of the lower esophageal sphincter (LES) has been taught by Soffer and Conklin(U.S. Pat. No. 8,160,709) to modulate the contraction of this smooth muscle sphincter. The primary application was to treat gastrointestinal reflux disease (GERD) by applying a pulse train of electrical stimulation to promote sustained contraction. The treatment of smooth muscle spasm using different stimulation parameters was also taught. Electrical stimulation of circular esophageal smooth muscle fibers such as the LES which is already contracted is known by those skilled in the art to lead to relaxation during the period of stimulation. In fact, electrical stimulation of some types of smooth muscle is known to involve non-cholinergic non-adrenergic (NANC) receptors which can lead to contractile responses opposite to the pre-stimulation state (Linden 1991). Thus, a pre-contracted smooth muscle can relax and a relaxed muscle can contract. The mechanism leading to this difference in response is unclear, but may involve the smooth muscle actin-myosin directly. Stimulation of NANC receptors through nerves is also possible except that the stimulation threshold of the structures involved must be significantly lower. Because this is a critical observation concerning the current inventive strategy, the data of (Linden 1991) is re-plotted in FIG. 1. What is shown in FIG. 1 is the dependence of contraction or relaxation responses depending on the resting tone level. A relaxing response to electrical stimulation of the airway smooth muscle is observed when resting tension is high and a contracting response from a lower resting tension. It is important to note that the responses were limited to NANC receptors by a drug induced block of the cholinergic receptors present normally. Further support of a relaxation response is the finding that following histamine induced bronchoconstriction, direct vagal nerve stimulation does lead to bronchial relaxation in animals and NANC receptor participation in promoting relaxation was postulated(Hoffinann 2009). NANC mediated responses are sensitive to the level of contraction prior to stimulation as well as stimulation parameters. For stimulation applications for fixed locations, such as the LES, electrical stimulation using electrodes can be an effective means of therapy. However, the location of the specific part of the gastrointestinal system needing treatment is not always the same and can even change as a function of time. Use of electrical stimulation always requires specific positioning of electrodes which limits application. Invasive implantation of stimulation electrodes and associated electronics is also required which is a significant and costly barrier to more widespread use for therapy. Temporary application of trancutaneous(skin surface)electrical stimulation (TENS) is known to those skilled in the art to be problematic for this application due to lack of specificity of what is stimulated. Pain fiber stimulation typically limit stimulation level below effective levels
Simon et al. (210130238049) proposed a transcutaneous electric nerve stimulator which was placed directly over the vagus nerve in the neck for stimulating vagus nerve afferent fibers for treatment of asthma. The relaxation of airway smooth muscle was the intended effect. Percutaneous (using needles through the skin) or direct electrical stimulation of the vagus nerve does lead to relaxation of airway smooth muscle as well as many other side effects since the vagus nerve affects most of the organs of the body. The most well known application of vagal stimulation is for epilepsy treatment. Obstructive sleep apnea has been reported as a major possible complication of this treatment. Transcutaneous stimulation level will always be limited by the pain produced by electrical current passing through the skin. So the effectiveness of this method is questionable and has yet to be shown.
Other features and advantages of the invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, various features of embodiments of the invention.